Identification of Epigallocatechin-3-Gallate as an Inhibitor of Phosphoglycerate Mutase 1

doi:10.3389/fphar.2017.00325

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Identification of Epigallocatechin-3-Gallate as an Inhibitor of Phosphoglycerate Mutase 1
	Li, Xiaoguang 1,2; Tang, Shuai 1; Wang, Qian-Qian 3; Leung, Elaine L. -H.3; Jin, Hongyue 1; Huang, Yongzhuo1 ; Liu, Jia1 ; Geng, Meiyu1 ; Huang, Min1 ; Yuan, Shengtao 2
刊名	FRONTIERS IN PHARMACOLOGY
	2017-05-30
卷号	8
关键词	phosphoglycerate mutase 1 (PGAM1) inhibitor cancer metabolism natural products anticancer activity
ISSN号	1663-9812
DOI	10.3389/fphar.2017.00325
文献子类	Article
英文摘要	Targeting metabolic enzymes is believed to provide new therapeutic opportunities for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that importantly coordinates glycolysis, pentose phosphate pathway (PPP) flux and serine biosynthesis in cancer cells and hence gains increasing interest of inhibitor discovery. Only few PGAM1 inhibitors have been reported and the molecular potency remains very limited. In an effort to discover new PGAM1 inhibitors, we carried out a biochemical assay-based screen that was focused on natural products derived small molecule compounds. (-)-Epigallocatechin-3-gallate (EGCG), the major natural catechins of green tea extract, was identified as a PGAM1 inhibitor that was tremendously more potent than known PGAM1 inhibitors. Further studies combining molecular docking and site-specific mutagenesis revealed that EGCG inhibited PGAM1 enzymatic activity in a manner independent of substrate competition. EGCG modulated the intracellular level of 2-phosphoglycerate, impaired glycolysis and PPP and inhibited proliferation of cancer cells. This study suggested EGCG as a chemical scaffold for the discovery of potent PGAM1 inhibitors and gained mechanistic insights to understand the previously appreciated anticancer properties of EGCG.
资助项目	China International Science and Technology Cooperation Program[2015DFM30040] ; Macao Science and Technology Development Fund[082/2013/A3] ; Macao Science and Technology Development Fund[086/2015/A3] ; Macao Science and Technology Development Fund[005/2014/AMJ] ; National Natural Science Foundation of China[81573464]
WOS关键词	GREEN TEA POLYPHENOL ; CANCER-CELLS ; GLUCOSE-METABOLISM ; LUNG-CANCER ; GLYCOLYSIS ; CARCINOMA ; TUMORS ; (-)-EPIGALLOCATECHIN-3-GALLATE ; TELOMERASE ; APOPTOSIS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000402269500001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272652]
专题	药理学第一研究室
通讯作者	Yao, Xiao-Jun; Ding, Jian
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China; 2.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing, Jiangsu, Peoples R China; 3.Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
推荐引用方式 GB/T 7714	Li, Xiaoguang,Tang, Shuai,Wang, Qian-Qian,et al. Identification of Epigallocatechin-3-Gallate as an Inhibitor of Phosphoglycerate Mutase 1[J]. FRONTIERS IN PHARMACOLOGY,2017,8.
APA	Li, Xiaoguang.,Tang, Shuai.,Wang, Qian-Qian.,Leung, Elaine L. -H..,Jin, Hongyue.,...&Ding, Jian.(2017).Identification of Epigallocatechin-3-Gallate as an Inhibitor of Phosphoglycerate Mutase 1.FRONTIERS IN PHARMACOLOGY,8.
MLA	Li, Xiaoguang,et al."Identification of Epigallocatechin-3-Gallate as an Inhibitor of Phosphoglycerate Mutase 1".FRONTIERS IN PHARMACOLOGY 8(2017).